A. Creatinine Phosphokinase (CPK) Elevation

1. Myocardial Infarction (Increased MB Fraction)
2. Cardiac troponin appears more sensitive indicator for cardiac damage than CPK
3. Myocardial Cell Death due to procedures (PCI)
4. Rhabdomyolysis (Crush injury; severe dehydration with muscle breakdown)
5. Muscular Dystrophy*
6. Inflammatory Myostitis*: Dermatomyositis / Polymyositis
7. Hoffman's Syndrome: myositis due to hypothyroidism
8. Muscle Trauma, Intramuscular Injection
9. Brain Infarction (stroke), Seizure, Neuroleptic Malignant Syndrome: BB fraction of CK
10. CK is produced by some Prostatic and Bronchogenic CAs
11. *Note that regenerating skeletal muscle often expresses the MB isozyme of CK

B. Cardiac Troponin Elevation [1]

1. Myocardial infarction (MI) - best test for ruling out MI
2. Nonthrombotic Myocardial Ischemia
   1. Coronary vasospasm
   2. Intracranial hemorrhage or stroke
   3. Sympathomimetic agent overdose
3. Demand Ischemia
   1. Sepsis / SIRS
   2. Severe hypotension or hypovolemia
   3. Supraventricular tachyarrhythmias
   4. Left ventricular hypertrophy
4. Direct Myocardial Damage
   1. Cardiac contusion
   2. Direct current cardioversion
   3. Chemotherapy
   4. Myocarditis / Pericarditis
   5. Cardiac infiltrative disorders (restrictive cardiomyopathies)
5. Myocardial Strain
   1. Congestive heart failure (CHF) - elevated troponin I or T associated with 2.6X mortality risk in acute cecompensated CHF [7]
   2. Pulmonary embolism
   3. Pulmonary hypertension or emphysema
   4. Strenuous exercise
6. Chronic renal insufficiency - unknown cause
7. Increases in troponins associated with overall increased risk of any cardiovascular mortality [8]

1. Over 30% of adults with initially elevated AST, ALT or bilirubin levels will be reclassified as normal on retesting [6]
2. Alcoholic Liver Disease (AST usually <4 fold elevated ; AST/ALT ratio >2)
3. Drug Related Hepatitis (partial list)
   1. Acetaminophen (Tylenol®, Paracetamol® and others) - even at recommended doses [4]
   2. Anti-Mycobacterial Agents: isoniazid, rifampin, rifampicin, rifamycin
   3. Tetracyclines
   4. Antifungal agents: griseofulvin, ketoconazole, fluconazole, itraconazole
   5. Trimethoprim-Sulfamethoxazole (TMP/SMX)
   6. Niacin
   7. HMG-CoA reductase inhibitors (statins)
   8. Nonsteroidal anti-inflammatory drugs (NSAIDS) - usually high dose
   9. Methotrexate (Rheumatrex® and others)
   10. Alpha-methyldopa
   11. Vitamin A
   12. Propylthiouracil (PTU)
   13. Halothane
   14. Various chemotherapy
   15. Herbal agents: Echinacea [5]
4. Acute Hepatitis 'Viral Hepatitis"
   1. Viral (Hepatitis A, B, C, E)
   2. Other Viruses (acute and chronic): EBV, CMV, adenovirus, HSV, Yellow Fever, VZV
   3. Drug Related
5. Chronic Hepatitis
   1. Chronic active viral hepatitis
   2. Chronic Autoimmune hepatitis
   3. Metobolic: Hemochromatosis, Wilson's Disease, alpha1-antitrypsin deficiency
6. Toxins: carbon tetrachloride, benzenes
7. Other infectious processes
   1. Focal Infections: Tuberculosis, MAI, Amoebiasis, Abscess (bacterial, fungal)
   2. Pneumonia (especially pneumococcal, legionella)
   3. Ascending Cholangitis
8. Vascular Disease
   1. Anoxia (hypotension) - Shock Liver (extremely high and rapid increase in LFTs)
   2. Budd-Chiari Syndrome
   3. Severe Right Sided Congestive Heart Failure
   4. Hepatic Venoocclusive Disease
9. Surgical / post-surgical (fibrotic) obstruction of biliary ducts
10. HELLP Syndrome (Pregnancy)
    1. Hemorrhage
    2. Elevated liver enzymes
    3. Low platelets
11. Total Parenteral Nutrition (TPN)
12. ALT is more specific for liver than AST
    1. AST elevated in erythrocyte hemolysis/destruction
    2. AST elevated in myocardial ischemia and infarction
    3. AST generally > ALT in alcoholic hepatitis

B. Alkaline Phosphatase Elevations

1. Differential below with little or no AST, ALT elevations
2. Liver (heat stable) and bone (heat labile) produce most of body's Alkaline Phosphate
3. Gallstone Related
   1. Cholelithiasis usually with jaundice
   2. Acute cholecystitis
4. Sclerosing cholangitis - predmoninantly male, many have Inflammatory Bowel Disease
5. Primary biliary cirrhosis - Majority of cases in middle aged (20-45) females
6. Steatosis: fatty liver (alcoholic, tetracyclines, pregnancy)
7. Cholangiocarcinoma
8. Infection or Tumor Infiltration in Bone or Liver
9. Granulomatous Disease
   1. Sarcoid
   2. Tuberculosis
   3. Fungal Infection
   4. Various hepatic granulomatous diseases
   5. Histiocytosis
10. 5'-nucleotidase (5'NT) is highly specific for liver cholestasis (obstruction)
11. Gamma-glutamyl transferase (GGT) is less specific and is inducible with drugs

1. Graves' Disesae
2. Multinodular goiter
3. Toxic nodule
4. Transient Thyroiditis
   1. Postpartum
   2. Silent (lymphocytic)
   3. Post-viral (granulomatous, subacute, DeQuervain's)
5. Thyroxine ingestion (rare)
6. Amiodarone therapy (rare)
7. Pregnancy Related: Gestational thyrotoxicosis, molar pregnancy

B. Low TSH, Normal Free T3/T4

1. Subclinical Hyperthryoidism
2. Thyroxine Ingestion
3. Rare
   1. Glucocorticoid Therapy
   2. Dopamine Infusion
   3. Dobutamine Infusion
   4. Non-thyroidal illness

C. Low or Normal TSH, Low Free T3/T4

1. Non-thyroidal illness
2. Recent treatment for hyperthyroidism
3. Rare
   1. Pituitary Disease (secondary hypothyroidism)
   2. Congenital TSH or TRH deficiency

D. Raised TSH, Low Free T3/T4

1. Primary Hypothyroidism
2. Common
   1. Chronic autoimmune thyroiditis
   2. Post-radioiodine
   3. Post-thyroidectomy
   4. Hypothyroid phase of transient thyroiditis
   5. If rapidly enlarging goiter, consider thyroid lymphoma
3. Rare
   1. Anti-thyroid peroxidase antibody negative; no radiation or surgery
   2. Drugs: amiodarone, lithium, interferons, interleukin-2, anti-CD52 (Campath)
   3. Idoine deficiency
   4. Amyloid goiter
   5. Reidel's thyroiditis
4. Congenital
   1. Thyroid tissue absent syndromes
   2. Thyroid tissue present - iodine transport or organification defects
   3. Thyroglobulin synthetic defect
   4. TSH-receptor defects

E. Raised TSH, Normal Free T3/T4

1. Subclinical autoimmune hypothyroidism (common)
2. Rare
   1. Interfering heterophile antibody
   2. Intermittent T4 therapy for hypothyroidism
   3. Drugs: amiodarone, sertraline, cholestyramine
   4. Recovery phase after non-thyroidal illness
3. Congenital
   1. TSH-receptor defects
   2. Resistance to TSH associated with other defects
   3. Pendred's Syndrome

References

1. Jeremias A and Gibson CM. 2005. Ann Intern Med. 142(9):767
2. Pratt DS and Kaplan MM. 2000. NEJM. 342(17):1266
3. Dayan CM. 2001. Lancet. 357(9256):619
4. Watkins PB, Kaplowitz N, Shattery JT, et al. 2006. JAMA. 296(1):87
5. Echinacea. 2002. Med Let. 44(1127):29
6. Lazo M, Selvin E, Clark JM. 2008. Ann Intern Med. 148(5):348
7. Peacock WF IV, De Marco T, Fonarow GC, et al. 2008. NEJM. 358(20):2117
8. Zethelius B, Berglund L, Sundstrom J, et al. 2008. NEJM. 358(20):2107